Cell cycle regulators in bladder cancer: A multivariate survival study with emphasis, on p27Kip1

Korkolopoulou, Penelope; Christodoulou, Panagiota; Konstantinidou, A. E.; Thomas-Tsagli, Euphemia; Kapralos, Panagiotis; Davaris, Panagiotis

doi:10.1053/hupa.2000.8227

Cited by 84 publications

(54 citation statements)

References 34 publications

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“…The choice of the biomarkers was based on previous studies estab- lishing their independent prognostic value in traditional multivariable analyses. [15][16][17][18][19][20][21][22][23][24][25][26][27][28] Moreover, these biomarkers are commonly used in pathology departments and most pathologists are familiar with immunohistochemical staining and interpretation of these biomarkers. However, combinations of other biomarkers reflecting the functional status of different pathways/phenomena associated with bladder cancer progression may provide similar or even greater predictive accuracy.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18][19][20][21][22][23][24][25][26][27] Several studies have shown that accumulation of altered expression of several of these immunohistochemical markers adds important prognostic information in patients treated with radical cystectomy. [15][16][17][18][19][20][21][22][23][24][25][26][27][28] A clinical trial is under way testing whether alterations of p53 nuclear expression can be used prospectively to identify high-risk patients and whether there is a benefit to administering adjuvant methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC) chemotherapy in p53-altered patients. 25,26,29 In the present study we hypothesized that the expression of a panel of established cell cycle regulators (ie, p53, pRB, p21, p27, and cyclin E1) could help identify patients with pTa-3 N0M0 UCB who are at increased risk for disease progression and therefore would be candidates for systemic adjuvant chemotherapy.…”

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confidence: 99%

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Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy

Shariat

Karakiewicz

Ashfaq

et al. 2007

Cancer

182

132

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BACKGROUND.Tested was whether the assessment of 5 established bladder cancer biomarkers (p53, pRB, p21, p27, and cyclin E1) could improve the ability to predict disease recurrence and cancer‐specific survival after radical cystectomy in patients with pTa‐3N0M0 urothelial carcinoma of the bladder (UCB).METHODS.The study comprised 191 patients with pTa‐3N0M0 UCB treated with radical cystectomy and bilateral lymphadenectomy (median follow‐up, 3.1 years). Biomarker expression was assayed on serial tissue microarray slides using quantitative immunohistochemistry using advanced cell imaging and color detection software. Predictive accuracy was quantified using the concordance index and 200‐bootstrap resamples were used to reduce overfit bias. Bootstrap‐adjusted predictive accuracy estimates were compared using the Mantel‐Haenszel test.RESULTS.UCB recurred in 36 (18.8%) patients and 30 (15.7%) died of bladder cancer; 157 (82.2%) patients had altered expression of at least 1 biomarker. In univariate analyses the number of altered biomarkers had the highest predictive accuracy for both disease recurrence (76.8%, P < .001) and cancer‐specific mortality (78.3%, P < .001). Addition of the number of altered biomarkers increased the predictive accuracy of nomograms based on the TNM staging system for disease recurrence and cancer‐specific mortality by 10.9% (83.4% vs 72.5%, P < .001) and 8.6% (86.9% vs 78.3, P < .001), respectively.CONCLUSIONS.Assessment of the number of altered biomarkers in the cystectomy specimen improves the prediction of bladder cancer recurrence and survival in patients with pTa‐3N0M0 disease. Prospective evaluation of alteration in these biomarkers can help identify patients who would benefit from adjuvant treatment after radical cystectomy. Cancer 2008. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy

Shariat

Karakiewicz

Ashfaq

et al. 2007

Cancer

182

132

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“…16 The observation that p27 does not necessarily lead to growth inhibition if LMW cyclin E is overexpressed may explain why the predictive potential of p27 levels has been controversial. Some studies have found that high p27 levels are associated with better clinical outcome, 28,29 while others have not found any prognostic Figure 3. Relationship between high LMW cyclin e protein expression and poor survival in bladder cancer.…”

Section: Methodsmentioning

confidence: 99%

Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer

et al. 2012

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“…Decreased levels of total p27 protein are associated with high tumor grade and stage in human breast (4,21), colorectal (7,57) and gastric cancer (81), among others. Reduction of p27 protein in tumors correlates significantly with decreased survival in breast (4,53,66), colorectal (34), gastric (39), ovary (38,42), prostate (9), bladder transitional cell (10,29) and esophageal squamous cell carcinoma patients (58), among others. These global findings regarding p27 expression in human cancers are significant, as it is highly unusual for a single molecular marker to have strong prognostic value in such a wide array of tumor types.…”

Section: History Of the 2-year Rodent Bioassaymentioning

confidence: 99%

p27 Kip1 (Cdkn1b)-Deficient Mice Are Susceptible to Chemical Carcinogenesis and May Be a Useful Model for Carcinogen Screening

Payne

Kemp

2003

Toxicol Pathol

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The two-year rodent bioassay is one of several tests that are widely used by governmental regulatory agencies as well as pharmaceutical and chemical companies to determine the carcinogenic potential of chemicals or environmental agents where human exposure is anticipated. That this assay has remained relatively unchanged for the last 25 years is a testament to the power of this approach to identify carcinogens and thus to minimize human exposure. However, there has long been controversy over the specificity and relevance of the rodent bioassay as well as its high cost in terms of time, expense, and numbers of mice. Much discussion has been generated in recent years over how to improve the 2-year rodent bioassay for more accurate and faster detection of potential human carcinogens. Here, we argue that the use of p27 Kip1 (Cdkn1b) knockout mouse for carcinogen screening may solve several shortcomings inherent in the conventional bioassay while preserving its best quality, that is, protecting public health by providing reliable in vivo information on the potential of chemicals to cause cancer.

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Cell cycle regulators in bladder cancer: A multivariate survival study with emphasis, on p27Kip1

Cited by 84 publications

References 34 publications

Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy

Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy

Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer

p27 Kip1 (Cdkn1b)-Deficient Mice Are Susceptible to Chemical Carcinogenesis and May Be a Useful Model for Carcinogen Screening

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